Data gathered during 1977 showed that there is close genetic linkage between the HLA system and the gene that confers susceptibility to juvenile diabetes mellitus (JDM). This linkage permitted us to uncover the fact that JDM is inherited as a recessive gene with about 50% penetrance. The goals for 1978 include the typing of families from rural areas, and from patients with age at onset of 16 and older. The purpose is to determine whether differences in the association data between New York and Europe are due to these variables. (We found DW3 increased but not DW4). If differences are found, we will determine whether the DW4-associated JDM gene displays the same genetic patterns. We will study the quantity and avidity of the insulin receptors in monocytes from JDM patients and their families, in order to define whether physiological alterations occur at this level.